Rheumatoid arthritis is a painful and debilitating inflammatory disorder with no known cure. It has been hypothesised that targeting the activity of RHO family proteins might be an effective therapeutic strategy, as these proteins are required for the function of macrophages, which contribute to immunopathology in arthritic joints. However, this notion is challenged in a recent paper by Khan et al. Unexpectedly, mice deficient for a key RHO-activating enzyme, geranylgeranyltransferase type I (GGTase-I), specifically in macrophages were found to develop spontaneous and severe joint inflammation resembling erosive rheumatoid arthritis. Macrophage-specific deficiency in GGTase-I was sufficient to induce pro-inflammatory signalling pathways and initiate the disease owing to sustained activation of RHO family proteins in macrophages. These data indicate that GGTase-I is not essential for the activity of RHO family proteins, and that inhibition of this enzyme can worsen, rather than prevent, the progression of rheumatoid arthritis.

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Eloise Mikkonen from the University of Tampere, Finland, is part of a collaborative project investigating a connection between herpes simplex virus and Alzheimer’s disease. Thanks to a Travelling Fellowship from DMM, she visited her collaborators in Umeå University, Sweden, and the team have now published their work in DMM. Read more on her story here.

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